Abstract
Propionibacterium acnes induction of inflammatory responses is a major etiological factor contributing to the pathogenesis of acne vulgaris. In particular, the IL-1 family of cytokines has a critical role in both initiation of acne lesions and in the inflammatory response in acne. In this study, we demonstrated that human monocytes respond to P. acnes and secrete mature IL-1β partially via the NLRP3-mediated pathway. When monocytes were stimulated with live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however, IL-1β secretion required only caspase-1 activity. P. acnes induced key inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL-1β secretion. The mechanism of P. acnes-induced NLRP3 activation and subsequent IL-1β secretion was found to involve potassium efflux. Finally, in acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous follicles and colocalized with tissue macrophages. Taken together, our results indicate that P. acnes triggers a key inflammatory mediator, IL-1β, via NLRP3 and caspase-1 activation, suggesting a role for inflammasome-mediated inflammation in acne pathogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology
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Adaptor Proteins, Signal Transducing / metabolism
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / immunology
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Apoptosis Regulatory Proteins / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism
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Caspase 1 / genetics
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Caspase 1 / metabolism
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Caspases / genetics
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Caspases / metabolism
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Cells, Cultured
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Gram-Positive Bacterial Infections / immunology*
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Humans
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Inflammasomes / genetics
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Inflammasomes / immunology
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Inflammasomes / metabolism
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Interleukin-1beta / immunology*
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Interleukin-1beta / metabolism
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Macrophages / cytology
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Macrophages / immunology
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Macrophages / microbiology
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Monocytes / cytology
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Monocytes / immunology*
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Monocytes / microbiology*
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLR Proteins
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Propionibacterium acnes / immunology*
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RNA, Small Interfering / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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Carrier Proteins
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IL1B protein, human
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLR Proteins
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NLRP1 protein, human
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NLRP3 protein, human
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RNA, Small Interfering
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CASP5 protein, human
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Caspases
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Caspase 1